1. Field of the Invention:
This invention relates to immunomodulation and immunodiagnosis.
2. Discussion of the Background:
This invention relates to the area of regulation of immune responsiveness in various disease states or in patients undergoing organ transplantations. It also relates to the area of immunogen development for naturally-occurring immunosuppressive factors associated with disease states (e.g., cancer, retroviral infections, viral infections, arthritis, etc.)
Immunological reactions can destroy neoplastic cells in vivo, and the accumulation of macrophages within a tumor can lead to its destruction. Cytotoxic T lymphocytes, natural killer (NK) cells, and activated macrophages can kill tumor cells in vitro. These observations suggest that the immune system provides some resistance against the development and spread of cancer, a contention strengthened by increased incidence of spontaneous tumors in individuals with congenital or acquired immune deficiency diseases.
In animals infected by tumor-producing retroviruses immunosuppression frequently precedes the development of tumors and a causal relationship is suspected between infection by the human retroviruses named T-cell lymphotropic virus III (HTLV III) or lymphadenopathy-associated retrovirus (LAV) and the development of the acquired immune deficiency syndrom (AIDS) and Kaposi's sarcoma.
Since immune mechanisms may limit the development or spread of cancer, clinically apparent tumors may develop when transformed cells acquire the means to escape immunological host defense mechanisms. In Immunology Today, Vol. 5, No. 8, 1984, pp. 240-244, Snyderman et al discuss factors produced by tumor cells which depress macrophage-mediated functions, and the recent observation that these substances may be related to the retroviral structural envelope protein p15E.
Snyderman et al conclude that whereas oncogene activation can induce neoplastic transformation, the expression of a p15E-like protein may allow transformed cells to escape immune destruction. They suggest that the immunosuppressive activity of p15E could be important in promoting tumorigenesis in vivo if transformed cells acquired the ability to synthesize this product. This reference, however, does not identify or even suggest which p15E-like protein would have any such immunosuppressive activity. It simply discloses that p15E is a hydrophobic transmembrane protein (around 19,000 daltons) of the retroviral envelope which is synthesized as part of a precursor of molecular weight 80,000-90,000.
Cianciolo et al, Nature, Vol. 311, October 11, 1984, p. 515, disclose that there is a certain homology between the various p15E proteins and human T-cell leukaemia-lymphoma viruses, HTLV-I and HTLV-II, which occurs in a 26-amino acid sequence located in the p21 region of HTLV.
Cianciolo et al note, in particular, that the first ten amino acids of the region having homology are identical, and that this region of homology occurs in almost the same region of the p15E and p21 molecules. They conclude that the significance of these types of regions occurring in murine, feline and human retroviruses is not clear. They note that since dramatic immunosuppression is often associated with these viruses and that purified p15E is immunosuppressive in a variety of systems, it would be of particular significance to determine whether p21 of HTLV can also inhibit immune functions. But they provide no clue with respect to which part of this region of homology or which segment may possess any immune activity.
Immune modulators have applications in various fields involving the immune system. For example, they are useful in preventing graft rejection, preventing autoimmunity, or in aleviating inflammatory reactions. Immune modulators which have thus far been used have however frequently not been fully effective and have suffered from numerous undesirable and substantial side effects.
There is thus a need for novel immune modulators having a wide variety of applications without suffering from undesirable side effects.